Mechanisms, function and clinical applications of DNp73

Abstract

p73, has two distinct promoters, which allow the formation of two protein isoforms: full-length transactivating (TA) p73 and an N-terminally truncated p73 species (referred to as DNp73) that lacks the N-terminal transactivating domain. Although the exact cellular function of DNp73 is unclear, the high expression levels of the genes have been observed in a variety of human cancers and cancer cell lines and have been connected to pro-tumor activities. Hence the aim of this review is to summarize DNp73 expression status in cancer in the current literature. Furthermore, we also focused on recent findings of DNp73 related to the biological functions from apoptosis, chemosensitivity, radiosensitibity, differentiation, development, etc. Thus this review highlights the significance of DNp73 as a marker for disease severity in patients and as target for cancer therapy.

Suppression of acetylpolyamine oxidase by selected AP-1 members regulates DNp73 abundance: mechanistic insights for overcoming DNp73-mediated resistance to chemotherapeutic drugs

“…Thus, DNp73 overexpression would be one mechanism of inhibiting TAp73-and p53-dependent pro-apoptotic activity in response to chemotherapeutic drugs, leading to poor clinical outcome. 12,13 Consistently, exposure to genotoxic signals leads to the upregulation of TAp73 and the downregulation of DNp73, 14 hence allowing an effective apoptotic response to ensue. This indicates that the relative abundance of the two forms of p73 could be an important determinant of cellular fate during stress response, thereby regulating chemosensitivity.…”

Diallyl disulfide enhances carbon ion beams–induced apoptotic cell death in cervical cancer cells through regulating Tap73 /ΔNp73

“…DNp73 is frequently overexpressed in multiple primary tumor types and cancer cell lines, but is barely detected in normal human tissues. 16 Schuster et al reported that DNp73 isoform apoptosis-related genes of the extrinsic and intrinsic apoptosis signaling pathways thereby contributing to chemoresistance. 45 In cervical cancer, it was shown that high expression levels of DNp73 have been shown to strongly correlate with poor survival of cancer and DNp73 positive tumors showed a reduced response to chemotherapy and irradiation.…”

“…The p73 locus encodes 2 types of transcription factors: full length pro-apoptotic isoforms (Tap73), and N-terminally truncated anti-apoptotic proteins (DNp73). 16 However, DNp73 are able to bind to DNA and to form dimers with Tap73, as well as with p53 and p63, thereby behaving as dominant negative, anti-apoptotic factors. 17 Additionally, DNp73 is frequently overexpressed in multiple primary tumor types and cancer cell lines, but is barely detected in normal human tissues.…”

microRNA Expression and Biogenesis in Cellular Response to Ionizing Radiation

“…Furthermore, we recently discovered that there was a differential DNp73 expression in response to different LET radiations, and downregulated DNp73 expression play a critical role in promoting cycle arrest and apoptosis in Hela cells (Di et al, , 2013. DNp73, as an antagonist to p53/ p63/TAp73, whether and how the downregulated DNp73 expression affects the miRNA biogenesis in cellular response to IR remains unknown.…”